ß-Sitosterol targets ASS1 for Nrf2 ubiquitin-dependent degradation, inducing ROS-mediated apoptosis via the PTEN/PI3K/AKT signaling pathway in ovarian cancer.

The exploration of drugs derived from natural sources holds significant promise in addressing current limitations in ovarian cancer (OC) treatments. While previous studies have highlighted the remarkable anti-cancer properties of the natural compound ß-sitosterol (SIT) across various tumors, its specific role in OC treatment remains unexplored. This study aims to investigate the anti-tumor activity of SIT in OC using in vitro and in vivo models, delineate potential mechanisms, and establish a preclinical theoretical foundation for future clinical trials, thus fostering further research. Utilizing network pharmacology, we pinpoint SIT as a promising candidate for OC treatment and predict its potential targets and pathways. Through a series of in vitro and in vivo experiments, we unveil a novel mechanism through which SIT mitigates the malignant biological behaviors of OC cells by modulating redox status. Specifically, SIT selectively targets argininosuccinate synthetase 1 (ASS1), a protein markedly overexpressed in OC tissues and cells. Inhibiting ASS1, SIT enhances the interaction between Nrf2 and Keap1, instigating the ubiquitin-dependent degradation of Nrf2, subsequently diminishing the transcriptional activation of downstream antioxidant genes HO-1 and NQO1. The interruption of the antioxidant program by SIT results in the substantial accumulation of reactive oxygen species (ROS) in OC cells. This, in turn, upregulates PTEN, exerting negative regulation on the phosphorylation activation of AKT. The suppression of AKT signaling disrupted downstream pathways associated with cell cycle, cell survival, apoptosis, migration, and invasion, ultimately culminating in the death of OC cells. Our research uncovers new targets and mechanisms of SIT against OC, contributing to the existing knowledge on the anti-tumor effects of natural products in the context of OC. Additionally, this research unveils a novel role of ASS1 in regulating the Nrf2-mediated antioxidant program and governing redox homeostasis in OC, providing a deeper understanding of this complex disease.

Single-cell analysis of the cellular landscape of vulvar melanoma provides new insight for immunotherapy administration.

BACKGROUND: Vulvar and vaginal melanoma (VuM & VaM) is a rare gynecologic malignancy with high mortality but low effectiveness to checkpoint immunotherapy compared to cutaneous melanoma. This article aims to elucidate the role of the disordered immune microenvironment in cancer progression in VuM. METHODS: At first, this article applied single-cell RNA sequencing (scRNA-seq) to the VuM obtained from a 68-year-old female patient, and constructed a single-cell atlas of VuM consist of 12,243 single cells. Then this article explores the genomic complexity and core signal channel in VuM microenvironment. RESULTS: This article provides new insights about the pathogenesis of VuM based on single-cell resolution data. It was found that the activation of CD8+ T cell contributed to induce tumor angiogenesis and immune escape, and the activation of the antigen-presenting molecular function participated in melanoma metastasis. CONCLUSION: This article provided new insights into underlining VuM molecular regulation and potential signaling involved in immunotherapy, which would benefit the clinical practice and administration.

PRICKLE1 gene methylation and abnormal transcription in Chinese patients with ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is a common inflammatory arthritis without a reliable biomarker. The role of methylation and mRNA expression of PRICKLE1 promoter in the pathogenesis of ankylosing spondylitis remains unclear. METHODS: A two-stage case-control design was used to detect the characteristics of methyl group and transcriptome of PRICKLE1 gene in Ankylosing spondylitis. The methylation degree of PRICKLE1 gene promoter region was tested by phosphate-sequencing, and further analyzed whether there was significant difference in methylation level of PRICKLE1 gene. The expression levels of PRICKLE1 mRNA in 50 AS patients and 50 healthy controls were detected by real-time quantitative PCR (RT-qPCR). RESULTS: Compared with healthy control group, the intensity of methylation in 4 ponds of PRICKLE1 in patients with Ankylosing spondylitis was low, and the mRNA levels were overexpressed (P = 0.017). ROC results showed that the sensitivity of PRICKLE1 was 68.67% and specificity was 71.43%. CONCLUSION: There is a significant change in the concentration of serum PRICKLE1 mRNA​in patients with Ankylosing spondylitis, and the degree of gene methylation is significantly reduced, suggesting that PRICKLE1 gene maybe involved in the pathogenesis of Ankylosing spondylitis, which may be useful for predicting the occurrence of AS and finding new early screening indicators.

A pregnant woman with a giant bilateral parietal hemangiopericytoma underwent multiple surgeries and radiotherapy: a case report and literature review.

Intracranial hemangiopericytoma is a rare invasive tumor originating from mesenchymal fibroblasts and is prone to local recurrence and distant metastasis. This study reports a case of a 27-year-old woman who presented with severe headache, nausea and vomiting for two weeks at thirty-three weeks of gestation. Cranial magnetic resonance imaging (MRI) demonstrated a giant lesion in the bilateral parietal lobe with a size of 5.12x9.19x6.03 cm and severe edema in the surrounding brain tissue. The patient underwent four operations and 3 gamma knife radiosurgery procedures and is recovering well now. The histopathology findings showed hemangiopericytoma and STAT6 and CD34 positivity after the first and second surgeries. Because of tumor progression, the patient received gamma knife radiosurgery at 1, 3, and 4 years after the first operation. Total tumor resection was achieved in the fourth surgery. Nevertheless, the patient showed malignant transformation to from low-grade to high-grade hemangiopericytoma.

Soy protein compared with whey protein ameliorates insulin resistance by regulating lipid metabolism, AMPK/mTOR pathway and gut microbiota in high-fat diet-fed mice.

The findings of soy protein versus whey protein supplementation on glycemic regulation are inconsistent. The aim of the present study was to investigate the preventive effect of soy protein isolate (SPI) and whey protein isolate (WPI) on a high-fat diet (HFD) induced insulin resistance and its potential molecular mechanisms. Male C57BL/6J mice were randomly divided into seven groups (n = 12): normal control, HFD plus 10% SPI, HFD plus 20% SPI, HFD plus 30% SPI, HFD plus 10% WPI, HFD plus 20% WPI, and HFD plus 30% WPI. After 12 weeks of feeding, compared with the WPI groups, serum concentration of insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and liver weight were significantly lower in the SPI groups. Compared with the WPI groups, the mRNA levels of CD36, SLC27A1, PPARγ and AMPKα were significantly higher, and those of LPL, SREBP1c, FASN and ACC1 were significantly lower in the liver in the SPI groups. In the liver or gastrocnemius muscle, compared with the WPI groups, the mRNA levels of GLUT4, IRS-1, PI3K and AKT were significantly higher, and those of mTOR and S6K1 were significantly lower, and the protein levels of GLUT4, p-AMPKα/AMPKα, p-PI3K/PI3K and p-AKT/AKT were significantly higher, and those of p-IRS-1Ser307/IRS-1, p-mTOR/mTOR and p-S6K1/S6K1 were significantly lower in the SPI groups. The Chao1 and ACE indices were higher, and the relative abundance of Staphylococcus and Weissella was lower in the SPI groups than those in the WPI groups. In conclusion, soy protein was more effective than whey protein in preventing IR in HFD-fed mice by regulating lipid metabolism, the AMPK/mTOR pathway, and gut microbiota.

Sonodynamic therapy combined with phototherapy: Novel synergistic strategy with superior efficacy for antitumor and antiinfection therapy.

Phototherapy (PT), including photodynamic therapy (PDT) and photothermal therapy (PTT), has recently achieved significant advances in antitumor and antiinfection therapy. Sonodynamic therapy (SDT), as a novel noninvasive therapy with a deeper penetration depth (>8 cm), fewer side effects and non-phototoxicity than PT, has drawn much attention in recent years. However, both PT and SDT have intrinsic limitations. By combining PT with SDT, the dualmodel therapy with advanced sensitizers overcome the intrinsic limitations and show higher efficacy than traditional monotherapy. Moreover, the photo-diagnosis modality could be easily integrated into synergistic therapy so that the sensitizer acts as a tracer for fluorescence/photoacoustic imaging, and the treatment process is visualized in a way that SDT combined with other therapies cannot achieve. This review summarizes the advanced sensitizers and the application of combination therapy, and explores the improvement strategies for promoting clinical transformation.

Stereotactic arrhythmia radioablation: A novel therapy for cardiac arrhythmia.

Cardiac arrhythmia is a global health problem, and catheter ablation has been one of its main treatments for decades. However, catheter ablation is an invasive method that cannot reach the deep myocardium, and it carries a considerable risk of side effects and recurrence. Therefore, it is necessary to explore a novel approach. Stereotactic body radiotherapy, which has been widely used in the field of radiation oncology, has recently expanded in the treatment of cardiac arrhythmia; when used in this context, it is known as stereotactic arrhythmia radioablation (STAR). As a noninvasive, effective, and well-tolerated treatment, STAR may be a suitable alternative method for patients with cardiac arrhythmia who are resistant or intolerant to catheter ablation. The main particles used to deliver energy in STAR are photons, protons, and carbon ions. Most studies have shown the short-term effectiveness of STAR, but problems such as a high long-term recurrence rate with a cumulative ventricular tachycardia-free survival rate from the published literature of 38.6% and related complications have also emerged. Therefore, in this article, we review the application of stereotactic body radiotherapy in cardiac arrhythmia, analyze its potential problems, and explore methods for improvement.

CLDN6 inhibits breast cancer metastasis through WIP-dependent actin cytoskeleton-mediated autophagy.

BACKGROUND: As a breast cancer suppressor gene, CLDN6 overexpression was found to inhibit breast cancer metastasis in our previous studies, but the specific mechanism remains unclear. This study aimed to clarify the role and mechanism of CLDN6 in inhibiting breast cancer metastasis. METHODS: Western blot, immunofluorescence and transmission electron microscopy were performed to detect autophagy. Wound healing, transwell assays and lung metastasis mouse models were used to examine breast cancer metastasis. Phalloidin staining and immunofluorescent staining were used to observe actin cytoskeleton. mRNA seq, RT-PCR, western blot, chromatin immunoprecipitation, dual luciferase reporter assay, co-immunoprecipitation and immunofluorescence were performed to define the molecular mechanism. The expression levels and clinical implication of CLDN6, WIP and LC3 in breast cancer tissues were evaluated using immunohistochemistry. RESULTS: We demonstrated that CLDN6 inhibited breast cancer metastasis through autophagy in vitro and vivo. We unraveled a novel mechanism that CLDN6 regulated autophagy via WIP-dependent actin cytoskeleton assembly. Through its PDZ-binding motif, overexpressed CLDN6 interacted with JNK and upregulated JNK/c-Jun pathway. C-Jun promoted WIP expression at the transcriptional level. Notably, we observed c-Jun transcriptionally upregulated CLDN6 expression, and there was a positive feedback loop between CLDN6 and JNK/c-Jun. Finally, we found that CLDN6, WIP and LC3 expression correlated with each other, and WIP expression was significantly associated with lymph node metastasis of breast cancer patients. CONCLUSIONS: The data provide a new insight into the inhibitory effects of CLDN6-mediated autophagy on breast cancer metastasis, and revealed the new mechanism of CLDN6 regulating autophagy through WIP-dependent actin cytoskeleton. Our findings enrich the theoretical basis for CLDN6 as a potential biomarker for breast cancer diagnosis and therapy.

Levels, distribution, sources and children health risk of PAHs in residential dust: A multi-city study in China.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are typical residential pollutants mainly from biofuel combustion that impose inevitable risk to children. The PAHs in residential dust is universal in most Chinese households with an obvious public health concern. METHODS: In this observational study, a total of 235 residential dust samples from 8 Chinese cities (Panjin, Shijiazhuang, Lanzhou, Luoyang, Xi'an, Wuxi, Mianyang, and Shenzhen) were collected from April 2018 to March 2019, which were extracted and analyzed for 16 priority PAHs by HPLC/FD-UV. Diagnostic ratios, hierarchical clustering analysis and principal component analysis were applied simultaneously for source apportionments. Incremental lifetime cancer risk was employed to estimate children's health risks based on the assumed exposure scenarios. Spearman correlation, Mann-Whitney U test, Kruskal-Wallis H test and Partial Least Squares were used to screen the factors affecting the concentration of PAHs in residential dust. RESULTS: The median concentration of ∑16PAHs in residential dust from 8 cities was 44.11 µg/g (0.04 - 355.79 µg/g). ∑16PAHs were found both higher in dust samples in heating season and from downwind households only in Mianyang (p < 0.05). The leading two sources of PAHs were combustion processes and automobile exhaust emissions based on four principal components that accounted for 74.29 % of the total variance. Indoor air environmental factors, household characteristics, and residents' behavioral lifestyles may be the influencing factors of residential dust PAHs. The carcinogenic risk of children aged 0 - 5 years, under the moderate exposure level of PAHs in residential dust, exceeded the acceptable level (10-5 - 10-4 for dermal contact and 10-6 - 10-5 for ingestion). CONCLUSIONS: There was serious PAHs pollution in residential dust under actual living conditions in eight cities across China. More evidence-based measures were needed to control PAHs pollution to safeguard children's health according to appointed sources and influencing factors in residential dust.

Simultaneous microwave-assisted phosphotungstic acid catalysis for rapid improvements on the accessibility and reactivity of Kraft-based dissolving pulp.

Improving the cellulose accessibility and reactivity in an efficient and convenient way has become the focused issue in the field of dissolving pulp manufacturing. We herein demonstrate a simple yet efficient strategy, namely a simultaneous microwave (MW)-assisted phosphotungstic acid (PTA) catalysis (MW-PTAsim). The MW-PTAsim treatment was efficient to improve Fock reactivity from 49.1 % to 85.8 % and decrease viscosity from 561 to 360 mL/g within 10 min, which was superior to the single MW treatment and the sequential MW-PTAseq treatment. Besides, the MW-PTAsim treated fiber had rougher and more fibrillated surfaces with an enhanced fiber accessibility, showing increased specific surface area (SSA) from 1.43 to 6.31 m2/g, mean pore diameter (MPD) from 6.92 to 11.20 nm and water retention value (WRV) from 101 % to 172 %. These positive enhancements are mainly due to a synergy that MW-enhanced rotation of PTA mediums was served as "spinning cutters" to attack the fibers, plus MW-accelerated PTA transfer and catalytic hydrolysis further improved the fiber accessibility. Moreover, PTA also demonstrates a high reusability and chemical stability. This process offers an effective and sustainable alternative for manufacturing a premium dissolving pulp.

The ignored risk: heavy metal pollution of medicine and food homologous substances.

A survey was conducted to investigate the effects of cadmium (Cd), arsenic (As), chromium (Cr), lead (Pb), and copper (Cu) in medicine and food homologous substances (MFHs) on human health. Nine common and typical MFHs (Dendrobium, Bulbus lilii, Poria, Semen nelumbinis, Radix puerariae, Gardenia jasminoides, Hordeum vulgare L, Semen coicis, and Ganoderma Karst) in the form of medicinal slices ready for decoction were purchased from pharmacies. Five among the MFHs (Dendrobium, Bulbus lilii, Poria, Semen nelumbinis, and Radix puerariae) were further obtained from a local field as raw materials for comparison. The results showed that raw materials of MFHs collected from the field had higher contents of heavy metal and greater health risks than medicinal slices purchased from pharmacy. Generally, the heavy metal residues in MFHs of different medicinal parts were different, and MFHs from roots or stems had significantly higher contents of heavy metals than those from fruits or seeds. Most importantly, the contents of Cd in Bulbus lilii and As in wild Poria from field were higher than the contents described in the Pharmacopoeia of the People's Republic of China (ChP). Non-carcinogenic and carcinogenic risk assessments revealed that Poria from field had larger non-carcinogenic and carcinogenic risks to human health; Bulbus lilii showed no non-carcinogenic risk but exhibited carcinogenic risks, whereas Cr showed carcinogenic risks in all samples. Given that MFHs are incorporated in regular foods, care should be taken to minimize health hazards caused by heavy metals to human. This study creates awareness on the safety issues associated with MFHs, and provides basic information for establishing the maximum allowable contents of medicinal and food substances in normal diets.

Tea consumption and risk of lower respiratory tract infections: a two-sample mendelian randomization study.

BACKGROUND: Observational studies have reported the association between tea consumption and the risk of lower respiratory tract infections (LRTIs). However, a consensus has yet to be reached, and whether the observed association is driven by confounding factors or reverse causality remains unclear. METHOD: A two-sample Mendelian randomization (MR) analysis was conducted to determine whether genetically predicted tea intake is causally associated with the risk of common LRTI subtypes. Genome-wide association study (GWAS) from UK Biobank was used to identify single-nucleotide polymorphisms (SNPs) associated with an extra cup of tea intake each day. The summary statistics for acute bronchitis, acute bronchiolitis, bronchiectasis, pneumonia, and influenza and pneumonia were derived from the FinnGen project. RESULTS: We found that genetically predicted an extra daily cup of tea intake was causally associated with the decreased risk of bronchiectasis [odds ratio (OR) = 0.61, 95% confidence interval (CI) = 0.47-0.78, P < 0.001], pneumonia (OR = 0.90, 95% CI = 0.85-0.96, P = 0.002), influenza and pneumonia (OR = 0.91, 95% CI = 0.85-0.97, P = 0.002), but not with acute bronchitis (OR = 0.91, 95% CI = 0.82-1.01, P = 0.067) and acute bronchiolitis (OR = 0.79, 95% CI = 0.60-1.05, P = 0.100). Sensitivity analyses showed that no heterogeneity and pleiotropy could bias the results. CONCLUSIONS: Our findings provided new evidence that genetically predicted an extra daily cup of tea intake may causally associated with a decreased risk of bronchiectasis, pneumonia, and influenza and pneumonia.

Association of indoor noise level with depression in hotel workers: A multicenter study from 111 China's cities.

Several studies have elucidated the link between outdoor noise and depression, but the relationship between indoor noise levels and depression symptoms in residential and public places remains unclear. This study was a multicenter observational study with a cross-sectional design. In 2019, a total of 10 545 indoor noise levels on-site and 26 018 health data from practitioners were collected from 2402 hotels in 111 cities. Indoor daily noise data levels were detected, and PHQ-9 questionnaires were used to collect health data. Logistic analysis was used to determine the association between depression score and noise level, negative binomial regression was used to determine potential risks. The geometric mean indoor noise level was 38.9 dB (A), with approximately 40.9% of hotels exceeding the 45 dB value (A). Approximately 19.1% of hotel workers exhibited mild and above depressive symptoms. In addition to functional zoning, geographic location, central air conditioner, decoration status, and other factors had an impact on noise levels (p < 0.05). Results of logistic and negative binomial regression showed the following: (1) there was significantly positive association between indoor noise and high depression scores above 2 (OR = 1.007, 95% CI: 1.002, 1.012) and (2) some sub-groups were more susceptible to this effect, especially for the younger female workers working in the first-tier cities, having higher education level, lower level of income, smoking, and longer working hours. This study confirms an early potential effect of indoor noise on depression. It is recommended to implement evidence-based measures to control noise sources in hotels.

The relationship of residential formaldehyde pollution in 11 Chinese cities to schoolchildren pneumonia prevalence in actual living condition.

Residential formaldehyde pollution is one of the leading residential harmful pollutants with a large production and consumption globally and remains much uncertainty in Chinese families with huge health burden for children worldwide. A multi-center observation study from 11 cities was conducted to investigate residential formaldehyde pollution levels measured by phenol reagent spectrophotometry. Data on household characteristics and schoolchildren's health were collected by questionnaire. The median concentration of residential formaldehyde was 0.025 (0.002-0.281) mg/m3 among 11 cities with the total exceeding standard rate of 7.40% according to the reference value of 0.10 mg/m3 (1-h average). Residential formaldehyde pollution in warm season, bedrooms and northern cities was more serious than that in cold season, living rooms and southern cities, respectively. The potential influencing factors of residential formaldehyde included household characteristics (distance from a traffic road, building history, residence duration, window glass layers, decoration and furniture) and use of air conditioner. The positive regulation effect of temperature on residential formaldehyde was explored with the approximately turning-point temperature of 28.9 °C for peak concentration. Long-term exposure to residential formaldehyde of low concentrations (0.010-0.090 mg/m3) would increase the prevalence of childhood pneumonia and a more stringent criteria value for residential formaldehyde should be discussed cautiously.

Pterostilbene attenuates RIPK3-dependent hepatocyte necroptosis in alcoholic liver disease via SIRT2-mediated NFATc4 deacetylation.

Receptor-interacting protein kinase (RIPK) 3-dependent necroptosis plays a critical role in alcoholic liver disease. RIPK3 also facilitates steatosis, oxidative stress, and inflammation. Pterostilbene (PTS) has favorable hepatoprotective activities. The present study was aimed to reveal the therapeutic effects of PTS on ethanol-induced hepatocyte necroptosis and further illustrate possible molecular mechanisms. Human hepatocytes LO2 were incubated with 100 mM ethanol for 24 h to mimic alcoholic hepatocyte injury. Results showed that PTS at 20 µM reduced damage-associated molecular patterns (DAMPs) release, including IL-1α and high-mobility group box 1 (HMGB1), and blocked necroptotic signaling, evidenced by decreased RIPK1 and RIPK3 expression. Trypan blue staining visually showed that PTS reduced nonviable hepatocytes after ethanol exposure, which was counteracted by adenovirus-mediated ectopic overexpression of RIPK3 but not RIPK1. Besides, PTS inhibited ethanol-induced hepatocyte steatosis via restricting lipogenesis and enhancing lipolysis, decreased oxidative stress via rescuing mitochondrial membrane potential, reducing oxidative system, and enhancing antioxidant system, and relieved inflammation evidenced by decreased expression of proinflammatory factors. Notably, RIPK3 overexpression diminished these protective effects of PTS. Subsequent work indicated that PTS suppressed the expression and nuclear translocation of nuclear factor of activated T-cells 4 (NFATc4), an acetylated protein, in ethanol-exposed hepatocytes, while NFATc4 overexpression impaired the negative regulation of PTS on RIPK3 and DAMPs release. Further, PTS rescued sirtuin 2 (SIRT2) expression, and SIRT2 knockdown abrogated the inhibitory effects of PTS on nuclear translocation and acetylation status of NFATc4 in ethanol-incubated hepatocytes. In conclusion, PTS attenuated RIPK3-dependent hepatocyte necroptosis after ethanol exposure via SIRT2-mediated NFATc4 deacetylation.

Polyaspartic acid alleviates cadmium toxicity in rapeseed leaves by affecting cadmium translocation and cell wall fixation of cadmium.

Polyaspartic acid (PASP) is a macromolecule compound with carboxylic acid side chains which is polymerized by L-aspartic acid, has been used as a biodegradable and environmentally-friendly chelating agent to enhance the phytoremediation of heavy metal-contaminated soils. Cadmium (Cd) is a toxic element for plant growth, productivity, and food security. To reveal the responses of PASP to plant physiology and morphology under Cd stress, we comprehensively analyzed soil characteristics, cell ultrastructure, reactive oxygen species (ROS), antioxidant enzymes, Cd uptake, transport, subcellular distribution, cell wall compositions, and their Cd chelating capacity in rapeseed. The results showed PASP increased the content of total N, total P, and available P in soil by 3.4%, 28.6%, and 39.8%, respectively, but did not change soil pH and available Cd. Meanwhile, PASP promoted dry mass accumulation and increased photosynthetic pigment content in rapeseed leaves by maintaining the chloroplast structure. Lower malondialdehyde (MDA) content and hydrogen peroxide (H2O2) accumulation and activated antioxidant enzymes in leaves indicate that PASP contributed to relieving Cd-induced oxidative damage to cells of rapeseed leaves. The results indicated that PASP application increased the Cd distribution ratio in root cell walls from 47.4% to 62.3% and decreased the Cd content in xylem sap by 37.8%, which ultimately reduced Cd reallocation in leaves. Additionally, higher pectin content and Cd in pectin resulted in higher Cd retention in leaf cell walls while reducing its concentration in the organelle fraction. The results indicated that 0.3% PASP effectively alleviated Cd stress in rapeseed leaves by inhibiting Cd transportation from roots, activating antioxidant enzymes to scavenge ROS, and promoting Cd chelation by cell wall pectin in leaves.

Source, Characterization of Indoor Dust PAHs and the Health Risk on Chinese Children.

Polycyclic aromatic hydrocarbons (PAHs) in indoor dust are one of the common exposure sources for children worldwide. The aim of this study is to explore PAHs pollution status in indoor dust and estimate health risk on Chinese children with big data. Weighted average concentration was used to analyze source and characterization of PAHs in indoor dust based on peer-reviewed literature. According to specific inclusion criteria, 17 studies were included finally to analyze weighted average concentration. The national average concentration of Σ16PAHs was approximately 25.696 µg/g. The highest concentration of Σ16PAHs was in Shanxi (2111.667 µg/g), and the lowest was in Hong Kong (1.505 µg/g). The concentrations in Shanxi and Guangdong were higher than national level and the over standard rate was 18.18%. The concentrations of individual PAHs varied greatly across the country, and Flu in Shanxi was the highest (189.400 µg/g). The sources of PAHs varied in different regions and combustion processes played a leading role. PAHs exposure through ingestion and dermal contact was more carcinogenic than inhalation. The incremental lifetime cancer risk model indicated that children lived in Shanxi were found in the highest health risk coupled with the highest BaPE concentration (54.074 µg/g). Although PAHs concentrations of indoor dust showed a downward trend from 2005 to 2018, indoor environmental sanitation should be improved with multidisciplinary efforts. Health standard should be possibly established to minimize children exposure to PAHs in indoor dust in China.

[Effect and Mechanism of Foliar Application Nano-MnO2 on Cadmium Enrichment of Rice].

Cadmium (Cd) is easily enriched in rice, resulting in an excessive Cd content in the grain, which seriously threatens human health. Manganese (Mn) is an essential element of plants. In a field experiment on Cd-contaminated acid soils, we investigated the effectiveness and mechanism of Mn in minimizing Cd accumulation in rice via foliar spraying using 0.1%, 0.3%, and 0.5% nano-MnO2 solutions at an early stage of heading. Compared with a control treatment, foliar spraying effectively reduced the Cd content of rice leaves, husks, and brown rice; increased the Mn content of all rice organs; but had no effect on rice yield. Foliar application of nano-MnO2 alleviated the plant stress induced by Cd by improving leaf photosynthesis, inhibiting lipid peroxidation, and increasing the content of the oxidative stress protein kinase. In addition, foliar application of nano-MnO2 limited the absorption of Cd by roots by increasing the content of iron-manganese plaque on the surfaces of rice roots and strengthening its adsorption/co-precipitation of Cd. Therefore, foliar application of nano-MnO2 during the early stages of rice heading is an effective measure to increase the Mn content and reduce the Cd content of brown rice.

CLDN6 Suppresses c-MYC-Mediated Aerobic Glycolysis to Inhibit Proliferation by TAZ in Breast Cancer.

Claudin 6 (CLDN6) was found to be a breast cancer suppressor gene, which is lowly expressed in breast cancer and inhibits breast cancer cell proliferation upon overexpression. However, the mechanism by which CLDN6 inhibits breast cancer proliferation is unclear. Here, we investigated this issue and elucidated the molecular mechanisms by which CLDN6 inhibits breast cancer proliferation. First, we verified that CLDN6 was lowly expressed in breast cancer tissues and that patients with lower CLDN6 expression had a worse prognosis. Next, we confirmed that CLDN6 inhibited breast cancer proliferation through in vitro and in vivo experiments. As for the mechanism, we found that CLDN6 inhibited c-MYC-mediated aerobic glycolysis based on a metabolomic analysis of CLDN6 affecting cellular lactate levels. CLDN6 interacted with a transcriptional co-activator with PDZ-binding motif (TAZ) and reduced the level of TAZ, thereby suppressing c-MYC transcription, which led to a reduction in glucose uptake and lactate production. Considered together, our results suggested that CLDN6 suppressed c-MYC-mediated aerobic glycolysis to inhibit the proliferation of breast cancer by TAZ, which indicated that CLDN6 acted as a novel regulator of aerobic glycolysis and provided a theoretical basis for CLDN6 as a biomarker of progression in breast cancer.

Application of different foliar iron fertilizers for enhancing the growth and antioxidant capacity of rice and minimizing cadmium accumulation.

Iron (Fe) fertilizer can reduce cadmium (Cd) uptake and toxicity in rice, but the underlying mechanisms of Cd mitigation by different fertilizers are poorly understood. Here, pot experiments in rice were conducted to characterize the effects of four types of foliar-applied Fe fertilizer (chelated ferrous Fe, ferric Fe, ionic ferrous Fe, and ferric Fe) at three doses (20, 50, and 100 mg L-1) on photosynthetic capacity, antioxidant ability, yield, and Cd accumulation in Cd-contaminated soil. The results showed that foliar Fe application increased the net photosynthesis rate by 19.3%, peroxidase (POD) by 18.2%, superoxide dismutase (SOD) by 26.9%, and catalase (CAT) by 19.6%, and led to a 7.2% increase in grain yield compared with the control. Moreover, foliar Fe application significantly reduced Cd accumulation by 15.9% in brown rice and decreased the translocation of Cd from roots to other plant tissues. Overall, application of moderate doses (50 mg L-1) of chelated ferrous Fe was the most effective method for reducing Cd uptake (decreasing the Cd concentration in brown rice by 29.0%) and toxicity in rice (decreasing malondialdehyde by 23.2% and increasing POD, SOD, and CAT by 54.4%, 51.6%, and 45.7%, respectively), which may stem from the fact that chelated ferrous Fe was a more stable and bioavailable source of Fe for rice. The Cd concentration in rice had negative relationship with Fe concentration, and the translocation of Cd from root to the other tissues was reduced by the higher Fe nutrition status in leaf, suggesting that a high Fe supply may decrease Cd content by inhibiting the expression of the Fe transport system. These results indicate that foliar application of chelated ferrous Fe provides a promising alternative approach for enhancing growth and controlling Cd accumulation in rice plants. Furthermore, these results advance our understanding of the associations between plant Fe nutrition status and Cd accumulation.